Carbapenems and penems are well known antibiotics for treating a broad range of gram-negative and gram-positive bacterial infections. ##STR1##
Methods and intermediates for the manufacture of carbapenems and penems are thus matters of scientific and commercial importance.
One method for the production of carbapenems is described in GB No. 2,162,840, Cainelli, et al. As described therein, certain carbapenems are produced from 4-acetoxyazetidin-2-one intermediates.
These intermediates are in turn produced in a multi-step synthesis from 4-alkenylazetidin-2-one intermediates of the formula: ##STR2## The starting materials to produce the 4-alkenylazetidin-2-one intermediates are: ##STR3## Thus, carbapenems may be produced through two principal intermediates from readily made or available starting materials. However, methods having fewer reaction steps to obtain the intermediates and improved yields are desirable.
Another method for the production of carbapenems is described in EPO No. 0167155, Kan, et al. Again, certain carbapenems are produced from 4-acetoxyazetidin-2-one intermediates. In this case however, these intermediates are in turn produced from 4-triorganosiloxyazetidin-2-one intermediates of the formula: ##STR4## The starting materials to produce the 4-triorganosiloxyazetidin-2-one intermediates are: ##STR5##
Thus, again, carbapenem may be produced through two principle intermediates from readily made or available starting materials. However, methods having fewer reaction steps to obtain the intermediates as well as methods using less hazardous starting materials than ClSO.sub.2 NCO are desired.
A method for the production of penems is disclosed in Christensen, et al., U.S. Pat. No. 4,260,618 from 4-acetoxyazetidin-2-one intermediates. Herein, it is recommended that these intermediates be produced by cleaving penicillin which is produced by fermentation.
It is an object of the present invention to produce 4-acyloxyazetidin-2-one intermediates useful in the production of carbapenems.
It is a further object of the present invention to produce 4-acyloxyazetidin-2-one intermediates from starting materials which are easily handled on account of their low levels of toxicity.
It is yet another object of the present invention to simplify the reactions required and improve the reaction yields in the production of 4-acyloxyazetidin-2-one intermediates.
It is still another object of the present invention to develop a method for the production of 4-acyloxyazetidin-2-one intermediates where an organic group is employed to protect the carbon in the 4-position of the azetidin-2-one and which subsequently may be converted to the 4-acyloxy substitution without replacement.